title: The vast majority of lymphocytes infiltrating primary cutaneous melanoma express the CD27 costimulatory receptor: implications for melanoma progression.
abstract: Melanoma progression is favoured by prevalence, within the micro-environment of primary cutaneous melanoma, of suppressive forces, e.g. exerted by CD4(+) CD25(+) FOXP3(+) regulatory T lymphocytes, over anti-melanoma immunity, e.g. exerted by CD8(+) cytolytic T lymphocytes. The CD27 glycoprotein is crucial because it is able to identify regulatory T cells endowed with strong suppressive ability, whilst CD8(+) T cells endowed with actual cytolytic ability become CD27(-). The present in situ quantitative immunohistochemical study, including a series of double labelling experiments and morphometrical cell analyses, shows that the vast majority of lymphocytes infiltrating primary cutaneous melanoma express CD27. Specifically, virtually the entire CD4(+) CD25(+) FOXP3(+) T subset infiltrating primary cutaneous melanoma also co-expressed CD27; CD27 was, moreover, co-expressed even by the vast majority of the CD8(+) T cells, and, conversely, effector/cytotoxic CD8(+)CD27(-) cells were very scarcely represented. The overwhelming CD27 co-expression may confer on the CD4(+)CD25(+)FOXP3(+) T subset a consistent capacity to suppress anti-melanoma immunity, whereas the too low CD8(+) CD27(-) cell proportion may presumably be insufficient to confer on the CD8(+) T subset a satisfactory anti-melanoma cytotoxic activity. We therefore propose that these CD27-discriminated pathways may trigger a functional imbalance within the microenvironment of primary cutaneous melanoma, thus favouring melanoma progression.
authors.affiliation: Section of Dermatology, Department of Surgical Sciences, Parma University, Via Gramsci 14, I-43100 Parma, Italy.
authors.forename: Carla Antonella
authors.initials: CA
authors.lastname: Pepe
authors.forename: Roberto
authors.initials: R
authors.lastname: Ricci
authors.forename: Chiara
authors.initials: C
authors.lastname: Cortelazzi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mori
authors.forename: Fabio
authors.initials: F
authors.lastname: Zambito
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Campanini
authors.forename: Francesca
authors.initials: F
authors.lastname: Aimi
authors.forename: Silvia
authors.initials: S
authors.lastname: Santoro
authors.forename: Mara
authors.initials: M
authors.lastname: Lombardi
authors.forename: Marcello
authors.initials: M
authors.lastname: Santini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: de Panfilis
mesh_terms: D003872:Dermatitis / Q000378:metabolism; D018450:Disease Progression; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016131:Lymphocyte Subsets / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7